TRIB3 alters endoplasmic reticulum stress-induced 尾-cell apoptosis via the NF-魏B pathway

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• 作者：Ni Fang^a ; ^b ; Wenjian Zhang^a ; Shiqing Xu^a ; Hua Lin^c ; Zai Wang^a ; Honglin Liu^a ; Qing Fang^a ; Chenghui Li^a ; Liang Peng^a ; ^{pengliang8028@163.com" class="auth_mail} ; Jinning Lou^a ; ^b ; ^{Lou.j@mail.com" class="auth_mail}
• 关键词：ER ; Endoplasmic reticulum ; iNOS ; Inducible nitric oxide synthase ; NF-魏B ; Nuclear factor-魏B ; NO ; Nitric oxide ; PDTC ; Pyrrolidine dithiocarbamate ; siRNA ; Small interfering RNA
• 刊名：Metabolism
• 出版年：June 2014
• 年：2014
• 卷：63
• 期：6
• 页码：822-830
• 全文大小：1446 K

文摘

To examine the effect of TRIB3 on endoplasmic reticulum stress induced 尾-cell apoptosis and to investigate the mechanism with a specific emphasis on the role of NF-魏B pathway.

Materials/Methods

We investigated the effect of TRIB3 on ER stress-induced 尾-cell apoptosis in INS-1 cells and primary rodent islets. The potential role of TRIB3 in ER stress inducer thapsigargin (Tg)-induced 尾-cell apoptosis was assessed using overexpression and siRNA knockdown approaches. Inducible TRIB3 尾-cells, regulated by the tet-on system, were used for sub-renal capsule transplantation in streptozotocin (STZ)-diabetic mice, to study the effect of TRIB3 on ER stress-induced 尾-cell apoptosis in vivo. Apoptosis was determined by TUNEL staining both in vivo and in vitro, while the molecular mechanisms of NF-魏B activation were investigated.

Results

TRIB3 was induced in ER-stressed INS-1 cells and rodent islets, and its overexpression was accompanied by increased 尾-cell apoptosis. Specifically, TRIB3 overexpression enhanced Tg-induced INS-1 derived 尾-cell apoptosis both in vitro and in sub-renal capsular transplantation animal model. Additionally, knockdown of Trib3 blocked Tg-induced apoptosis. Mechanistically, the induction of TRIB3 during ER stress resulted in the activation of NF-魏B and aggravated INS-1 derived 尾-cell apoptosis, while inhibiting the NF-魏B pathway significantly abrogated this response and prevented 尾-cell apoptosis, both in vitro and in sub-renal capsular transplantation animal model.

Conclusion

TRIB3 mediated ER stress-induced 尾-cell apoptosis via the NF-魏B pathway.